Aliment Pharmacol Ther, 1999 Jun, 13(6), 741 - 6 Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection-comparison with omeprazole and lansoprazole; Miwa H et al.; BACKGROUND: A recent trend in curative therapy for Helicobacter pylori infection is the so-called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials . Various regimens employing this triple therapy have been reported . However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy . AIM: To validate its usefulness by comparing rabeprazole with omeprazole and lansoprazole, in combination with amoxycillin and clarithromycin . PATIENTS AND METHODS: 221 H . pylori-positive patients with peptic ulcer disease were randomized to receive one of three different proton pump inhibitor/amoxycillin-clarithromycin (PPI/AC) regimens for 7 days . (i) OAC regimen (n = 75): omeprazole 20 mg b.d., amoxycillin (AMOX) 500 mg t.d.s . and clarithromycin (CAM) 200 mg b.d.; (ii) LAC regimen (n = 74): lansoprazole 30 mg b.d . , AMOX 500 mg t.d.s . and CAM 200 mg b.d.; and (iii) RAC regimen (n = 72): rabeprazole 20 mg b.d., AMOX 500 mg t.d.s . and CAM 200 mg b.d . Cure of the infection was determined by the 13C urea breath test 1 month after completion of the treatment . RESULTS: Intention-to-treat based cure rates for OAC, LAC and RAC regimens were 85% (95% CI, 75-92), 84% (95%, CI 73-91) and 88% (95% CI, 78-94), respectively, and per protocol based cure rates of these regimens were 88% (95% CI, 78-94), 91% (95%, CI 82-99) and 93% (95% CI, 84-98), respectively . Adverse effects in the entire study population, which included diarrhoea, glossitis or skin rash, were reported by 15% of the patients, and complete compliance was achieved in 95% of these patients . CONCLUSION: 1-week proton pump inhibitor/AC regimens for H . pylori infection were effective in the Japanese population . Rabeprazole can be considered as equivalent to omeprazole and lansoprazole in the PPI/AC triple therapy. J Antimicrob Chemother, 1999 May, 43(5), 711 - 4 In-vitro activity of grepafloxacin, a new fluoroquinolone, against mycoplasmas; Bebear CM et al.; The in-vitro activity of grepafloxacin, a new oral fluoroquinolone antibiotic, was compared with those of three other fluoroquinolones and two unrelated antimicrobials, doxycycline and erythromycin, against various Mycoplasma spp . For 65 mycoplasma and 42 ureaplasma strains, grepafloxacin (MIC range 0.03-2 mg/L) was some two to 16 times more active than ofloxacin and ciprofloxacin, showing similar activity to that of sparfloxacin . MBCs of grepafloxacin increased two- to 16-fold when compared with MICs and were comparable to those of sparfloxacin, and lower than those of ofloxacin and ciprofloxacin. J Clin Periodontol, 1999 Jun, 26(6), 341 - 6 Microbiological and clinical effects of an antiseptic dental varnish after mechanical periodontal therapy; Dudic VB et al.; The aim of this study was to explore the microbiological and clinical effects of an antiseptic dental varnish when applied to periodontally diseased teeth after mechanical therapy . 20 subjects participated in this placebo controlled, double blind prospective longitudinal study . 2 experimental sites with a pocket probing depth > or =5 mm were chosen in each subject . The control varnish, consisting of ethanol, ethylacetate and polyvinylbutyral, was applied to one of the selected teeth and the test varnish, containing 1% chlorhexidine and 1% thymol in addition, was applied to the other one . Clinical parameters were assessed, and microbiological samples were obtained from the two study sites at baseline (6-10 weeks after completion of conventional periodontal therapy), and 2, 4 and 12 weeks thereafter . The mean PLI at baseline was very low and, therefore, only a minimal potential for a further improvement existed . During the 12-week observation period, the mean PLI increased significantly at sites treated with the placebo varnish, while no similar trend for an increase in PLI was detected in the test sites . The bleeding tendency seemed to remain unaffected by the application of the varnish . On the microbiological level, no relevant differences could be detected between placebo and test sites at baseline, or during the follow-up period . In conclusion, the application of a dental varnish with antimicrobial properties after mechanical periodontal therapy had little effect in subjects with good oral hygiene. Scand J Rheumatol, 1999, 28(3), 157 - 9 Adverse drug reactions in Sjögren's syndrome . Frequent allergic reactions and a specific trimethoprim-associated systemic reaction; Antonen JA et al.; Trimethoprim-associated systemic reactions, including aseptic meningitis, have been reported to be very rare adverse drug reactions . Patients with Sjogren's syndrome have been overrepresented, but no epidemiological surveys of the reaction have been conducted . To study the overall frequency of adverse drug reactions, and especially trimethoprim-associated reactions, we interviewed 85 primary Sjogren's syndrome patients and compared the results with those of 45 similarly interviewed osteoarthritis patients . Antimicrobial allergy was more common among Sjogren's syndrome patients than in osteoarthritis patients (46% vs . 27%) . Eleven Sjogren's syndrome patients (13%), but no osteoarthritis patient, had experienced at least a partial, non-allergic systemic reaction with trimethoprim . Of them five (6%) had had a full-blown systemic reaction including both chills/fever and headache/backache and at least one of the following: malaise, vomiting, dizziness, confusion or meningeal irritation . Our findings confirm that allergic reactions to antimicrobials are frequent in Sjogren's syndrome . In addition to allergic reactions Sjogren's syndrome patients are prone to a specific trimethoprim-associated systemic reaction . This should be remembered when prescribing antimicrobials. Biosci Biotechnol Biochem, 1999 May, 63(5), 955 - 7 Inhibition of iron/ascorbate-induced lipid peroxidation by an N-terminal peptide of bovine lactoferrin and its acylated derivatives; Wakabayashi H et al.; Bovine lactoferrin (LF) and lactoferricin B (LFcin B), an antimicrobial peptide derived from bovine LF, inhibited thiobarbituric acid-reactive substance (TBARS) formation in a iron/ascorbate-induced liposomal phospholipid peroxidation system . The inhibition of TBARS formation occurred with N-acylated 9-mer peptides with a core sequence of LFcin B and, compared to LFcin B, their antioxidant effect was clearly observed at a concentration almost 100 times lower. Infection, 1999, 27 Suppl 1, S56 - 60 Reduced rates of catheter-associated infection by use of a new silver-impregnated central venous catheter; Boswald M et al.; A central venous catheter with a new form of silver impregnation of the internal and external surfaces was investigated for antimicrobial activity and tolerance in patients in a controlled comparative, prospective and randomized clinical study . Commercially available catheters with no antimicrobial activity were used as controls . One hundred sixty-five catheters were included in the final evaluation . All catheters were percutaneously inserted for the first time with a duration of > or = 5 days and a microbiological examination of the catheter tip . Catheter location (> 90% internal jugular vein), mean duration of catheterization (8-9 days), patients' age and diagnosis were comparable in both groups . Silver-impregnated catheter tips showed an incidence of colonization in 14.2/1000 catheter days and control catheters in 22.8/1000 catheter days . This represents a reduction of 37.7% . Catheter-associated infections were diagnosed in the silver group in 5.26/1000 catheter days and 18.34/1000 catheter days in the control group, indicating a reduction rate of 71.3% (P < 0.05, chi 2-test) . No complications or side effects were documented in either group. Infection, 1999, 27 Suppl 1, S43 - 5 Thermoplastic polyurethane--the material used for the Erlanger silver catheter; Hentschel T et al.; The Erlanger silver catheter consists of a thermoplastic polyurethane elastomer (TPU) . To achieve an antimicrobial effect, silver particles at a concentration of 0.5-1.0% by weight are incorporated into the basic material . The good mechanical properties were shown to remain present after the incorporation of the silver . The characteristic mechanical data of blends made of a soft and a hard TPU type approximated closely to a linear relationship with the ratio of the mixture . The buckling stability of catheters as a function of their cross section could be described by Euler's formula . This enables the buckling stability to be calculated when material constants and catheter geometry are known. Infection, 1999, 27 Suppl 1, S16 - 23 A new technology of microdispersed silver in polyurethane induces antimicrobial activity in central venous catheters; Guggenbichler JP et al.; Metal ions or metal ions in complexes or compounds have been used for centuries to disinfect fluids, solids and tissues . The biocidal effect of silver, with its broad spectrum of activity including bacterial, fungal and viral agents, is particularly well known and the term "oligodynamic activity" was coined for this phenomenon . Silver ions have an affinity to sulfhydryl groups in enzyme systems of the cell wall, through which they interfere with the transmembranous energy transfer and electron transport of bacterial microorganisms . Silver ions also block the respiratory chain of microorganisms reversibly in low concentrations and irreversibly in higher concentrations . Binding to the DNA of bacteria and fungi increases the stability of the bacterial double helix and thus inhibits proliferation . There is no cross resistance with antibiotics and also no induction of antimicrobial resistance by silver ions . The concentrations required for bactericidal activity are in the range 10(-9) mol/l . These concentrations can be achieved in solution by the interaction of metallic silver with electrolytes only if there is a large enough surface of silver . By a novel technology, metallic silver is distributed in submicron particles in polyurethane and results in a concentration of 0.8% in an active surface of 450 cm2/g polyurethane . Polyurethane is hygroscopic and rapidly attracts water; the interaction of electrolyte solutions with the extremely finely distributed silver throughout the polyurethane releases bactericidal concentrations of silver ions over a period of years to the surface of the material . The electronegatively charged surface of bacteria attracts the positively charged silver ions . The concentrations released from the polyurethane are far below the toxic concentrations for humans. Pract Periodontics Aesthet Dent, 1999 Apr, 11(3), 343 - 5 Aerosol and vapor control in the dental treatment room; Young JM; As dental clinicians, common sense is still the best weapon for infection control--the use of antimicrobial cleaning products remains an integral component of any infection control procedure. Zentralbl Veterinarmed B, 1999 May, 46(4), 261 - 9 Experimental infections with Actinobacillus pleuropneumoniae in pigs--II . Comparison of antibiotics for oral strategic treatment; Wallgren P et al.; The present study was aimed at scrutinizing the efficacy of oral antimicrobial treatments at experimental challenge using a strain of Actinobacillus pleuropneumoniae serotype 2 known to cause severe disease . SPF pigs aged 10 weeks were infected intranasally and the antimicrobial treatments were initiated 5 h prior to that exposure . Several antimicrobial drugs, as well as the length of the treatment period, were elucidated . The outcome of the challenge was monitored by registration of clinical symptoms, weight gains and the development of serum antibodies to A . pleuropneumoniae . At necropsy, the magnitude of pathological lesions in the respiratory tract and the rate of reisolation of the infective strain were recorded . Animals that became diseased displayed a decreased growth rate caused, to a large extent, by a reduced feed intake . The performance with respect to daily weight gain and feed conversion corresponded well with the clinical signs developed and serologic reactions, as well as with the findings made at necropsy . The results obtained among pigs treated with enrofloxacin, but also with florfenicol or chlortetracycline, were superior to those of pigs treated with penicillin, tiamulin or tilmicosin . A positive effect was obtained using a strategic in-feed medication against infection with A . pleuropneumoniae . Provided that the drug used is effective against the target microbe, initiating treatment prior to infection appeared to be more important than the length of the treatment . It should, however, be remembered that A . pleuropneumoniae was reisolated from all but one medicated group following an experimental challenge given after initiating the medication . Consequently medical treatment as described did not eradicate the microbe. Pharmacol Res, 1999 Jul, 40(1), 41 - 6 Spontaneous reporting of adverse drug reactions in elderly patients in Sicily (Italy); Cutroneo P et al.; The aim of this study was to investigate the spontaneous reports of suspected adverse drug reactions, observed in elderly patients (over 65 years of age) in Sicily (Italy) during the period from 1 January 1995 to 31 December 1997 . Of 1307 reports, the geriatric ADRs were 284 (21.7%); 92 (32.4%) of these were serious . There was a correlation between the reporting rates of ADRs and the increase of age . Similar trends are seen in the number of serious ADR reports . Old-older patients result most frequently affected by serious ADRs . The antimicrobial and musculo-skeletal drugs were responsible for 48 . 3% of the whole suspected geriatric ADRs . The commonest ADRs reported for the elderly, affected skin and the gastrointestinal system . There was probably a correlation between multi-drug consumption, comorbidity and seriousness of ADRs . A higher percentage of serious ADRs originated from university hospitals (57 . 1%) . Structure Fold Des, 1999 May, 7(5), 489 - 96 Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents; Xiao B et al.; BACKGROUND: Folate cofactors are essential for life . Mammals derive folates from their diet, whereas most microorganisms must synthesize folates de novo . Enzymes of the folate pathway therefore provide ideal targets for the development of antimicrobial agents . 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway . RESULTS: The crystal structure of HPPK from Escherichia coli has been determined at 1.5 A resolution with a crystallographic R factor of 0.182 . The HPPK molecule has a novel three-layered alpha beta alpha fold that creates a valley approximately 26 A long, 10 A wide and 10 A deep . The active center of HPPK is located in the valley and the substrate-binding sites have been identified with the aid of NMR spectroscopy . The HP-binding site is located at one end of the valley, near Asn55, and is sandwiched between two aromatic sidechains . The ATP-binding site is located at the other end of the valley . The adenine base of ATP is positioned near Leu111 and the ribose and the triphosphate extend across and reach the vicinity of HP . CONCLUSIONS: The HPPK structure provides a framework to elucidate structure/function relationships of the enzyme and to analyze mechanisms of pyrophosphoryl transfer . Furthermore, this work may prove useful in the structure-based design of new antimicrobial agents. Acta Chem Scand, 1999 Jun, 53(6), 446 - 52 Preparation and antimicrobial studies of acyclic sulfamates; Gautun HS et al.; A series of acyclic sulfamates have been prepared and tested for antimicrobial activity . Thus, the oxysulfonyl isocyanates, ROSO2NCO (1a, R = 4-methoxyphenyl; 1b, R = phenyl; 1c, R = 4-chlorophenyl and 1d, R = 2,2,2-trifluoroethyl) have been prepared in 76-91% yield from chlorosulfonyl isocyanate . Treatment of 1a-d with glycidol gave the glycidyl carbamates 2a d . Internal cyclisation afforded the corresponding 4-hydroxymethyl-2-oxazolidinones 3a-d, which in turn were hydrolysed to give the free amino alcohols 4a-d . The yields were in the range 39-85% . A preliminary agar diffusion test of 2a-d, 3a-d, 4a-d indicated 2a-d and 3c to be possible antimicrobial agents . A more thorough analysis of these compounds revealed a minimum inhibition concentration (MIC) of 128 and 64 mg l-1 for glycidyl p-methoxyphenoxysulfonylcarbamate (2a) and glycidyl phenoxysulfonylcarbamate (2b) respectively, against Branhamella catarrhalis. Mol Med Today, 1999 Jul, 5(7), 292 - 7 Antibiotic peptides from higher eukaryotes: biology and applications; Ganz T et al.; Gene-encoded antibiotic peptides are increasingly being recognized as effector molecules of host defense in plants and animals . Studies of antimicrobial peptides are providing new insights into the dynamic interactions between microbes and their hosts, and are generating new paradigms for the pathogenesis and treatment of diseases . Because antimicrobial peptides of higher eukaryotes differ structurally from conventional antibiotics produced by bacteria and fungi, they offer novel templates for pharmaceutical compounds that could be effective against increasingly resistant microbes. Infect Immun, 1999 Jul, 67(7), 3610 - 8 Resistance of virulent Mycobacterium avium to gamma interferon-mediated antimicrobial activity suggests additional signals for induction of mycobacteriostasis; Florido M et al.; The cytokine gamma interferon (IFN-gamma) plays a major role in the control of Mycobacterium avium infections . We assessed whether the progressive growth of virulent strains of M . avium was associated with alterations in the production of this cytokine as evaluated by reverse transcription-PCR and detection of immunoreactive cytokine in the serum and in spleen homogenates . We found that IFN-gamma was induced during infection by a virulent strain of M . avium to similar or even higher extents than the levels found during infections by a less virulent strain whose growth was controlled . IFN-gamma produced during infection by both mycobacterial strains was partly derived from T cells and led to activation of macrophages, namely, those that were infected . Concomitant with the development of the infection with the virulent strain of M . avium there was an extensive depletion of lymphocytes in the spleen . Thymectomy alone promoted the proliferation of the virulent, but not of the less virulent, strain of M . avium . Our data indicate that virulent strains of M . avium resist the antimicrobial mechanisms of IFN-gamma-activated macrophages and raise the possibility that a second, T-cell-dependent signal is required for the effective control of mycobacterial replication inside macrophages. Infect Immun, 1999 Jul, 67(7), 3199 - 206 Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages; Gomes MS et al.; Despite the antimicrobial mechanisms of vertebrate phagocytes, mycobacteria can survive within the phagosomes of these cells . These organisms use various strategies to evade destruction, including inhibition of acidification of the phagosome and inhibition of phagosome-lysosome fusion . In contrast to mycobacteria, Coxiella burnetii, the etiologic agent of Q fever, inhabits a spacious acidified intracellular vacuole which is prone to fusion with other vacuoles of the host cell, including phagosomes containing mycobacteria . The Coxiella-infected cell thus provides a unique model for investigating the survival of mycobacteria in an acidified phagosome-like compartment . In the present study, murine bone marrow-derived macrophages were infected with either Mycobacterium avium or Mycobacterium tuberculosis and then coinfected with C . burnetii . We observed that the majority of phagocytosed mycobacteria colocalized to the C . burnetii-containing vacuole, which maintained its acidic properties . In coinfected macrophages, the growth of M . avium was not impaired following fusion with the acidified vacuole . In contrast, the growth rate of M . tuberculosis was reduced in acidified vacuoles . These results suggest that although both species of mycobacteria inhibit phagosome-lysosome fusion, they may be differentially susceptible to the toxic effects of the acidic environment in the mature phagolysosome. Am J Vet Res, 1999 Jun, 60(6), 669 - 75 Superoxide production in phagocytes obtained from Mycobacterium marinum-stimulated goldfish (Carassius auratus) that were exposed to copper; Jacobson SV et al.; OBJECTIVE: To investigate the effects of copper exposure and recovery from copper toxicosis on the nonspecific immune response in Mycobacterium marinum-inoculated goldfish . ANIMALS: Goldfish (Carassius auratus) with a mean weight of 33.5 g . PROCEDURE: Superoxide (O2-) production was measured in fish 2 to 6 weeks after injection with phosphate-buffered saline (PBS) solution or M marinum (10(2) to 10(7) colony-forming units {CFU}/fish) . Then, paired groups of fish were injected with PBS solution or 10(4) CFU of M marinum and exposed to copper (100 microg/L) for 7 days or for 4 days with 3 days of recovery . One paired group not exposed 14 days later to copper served as control fish . Phagocyte production of O2-was measured by use of the nitroblue tetrazolium reduction assay . Inflammation and bacterial colony counts were determined by use of routine histologic and microbiologic procedures . RESULTS: Superoxide production achieved a maximal response 2 to 4 weeks after M marinum inoculation . Compared with control fish, O2- production increased in the groups exposed to copper but then decreased in the exposed groups that were allowed to recover . Superoxide response and peritoneal inflammation were greater in M marinum-inoculated groups than in non-inoculated groups . CONCLUSIONS: Copper exposure and inoculation with M marinum increased O2- production, whereas recovery after exposure decreased O2- production, even in fish that were immunostimulated by M marinum . CLINICAL RELEVANCE: When the antimicrobial oxidative response is suppressed after copper exposure, steps should be taken to avoid imposing additional stress and minimize the possibility of resurgent or secondary pathogenic infections. J Trauma, 1999 Jun, 46(6), 1078 - 81 Wound infections after minor limb lacerations: risk factors and the role of antimicrobial agents; Stamou SC et al.; BACKGROUND: The requirement for antimicrobial agents in patients with minor limb lacerations was prospectively studied . METHODS: The development of wound infections in patients with minor limb lacerations who received amoxicillin plus clavulanate acid treatment (group A, 52 patients) was studied and compared with patients who did not (group B, 48 patients) . RESULTS: Wound infection occurred in 6 (11.5%) and 10 (21%) patients in groups A and B, respectively (p>0.10) . Statistically significant risk factors for the development of infection were diabetes mellitus (odds ratio {OR}, 15.8; p<0.001), lower limb lacerations (OR, 33.5; p<0.001), lacerations caused by compressive forces (OR, 21.6; p = 0.007), laceration length from 5 to 8 cm (OR, 7.04; p = 0.001), ragged laceration edge (OR, 2.55; p = 0.049), and skin tension (OR, 2.00; p = 0.006) . CONCLUSION: The use of antimicrobial agents in minor limb injuries was not associated with a significant reduction of infection rate . Routine antimicrobial treatment is discouraged. Compend Contin Educ Dent, 1998 Oct, 19(10), 953 - 6; 958, 960 passim quiz 966 Local delivery of antimicrobial agents for the treatment of periodontitis; Magnusson I; Periodontitis is a result of an infection with specific pathogenic microorganisms . Thus, the local delivery of antimicrobials has been investigated as a possible method for controlling this infection and treating periodontal disease . A number of antimicrobial agents have been studied both as adjunctive therapies with scaling and root planing and as stand-alone chemotherapies . These agents have been administered in irrigation solutions and as single-dose formulations, but with little long-term efficacy in the treatment of periodontitis . Recent investigations have focused on the delivery of antimicrobials in sustained-release formulations designed to maintain effective concentrations of drug within the periodontal pocket . This article provides an overview of the development of the use of locally delivered antimicrobials in periodontal therapy and the current state-of-the-art of the technique. FEBS Lett, 1999 May 28, 451(3), 235 - 7 Human milk lactoferrin binds two DNA molecules with different affinities; Kanyshkova TG et al.; Evidence is presented that lactoferrin (LF), an Fe3+-binding glycoprotein, possesses two DNA-binding sites with different affinities for specific oligonucleotides (ODNs) (Kdl = 8 nM; Kd2 approximately 0.1 mM) . The high affinity site became labeled after incubation with affinity probes for DNA-binding sites; like the antibacterial and polyanion-binding sites, this site was shown to be located in the N-terminal domain of LF . Interaction of heparin with the polyanion-binding site inhibits the binding of ODNs to both sites . These data suggest that the DNA-binding sites of LF coincide or overlap with the known polyanion and antimicrobial domains of the protein. Farmaco, 1999 Mar 31, 54(3), 161 - 8 Synthesis of 3,6,7-substituted-quinoxalin-2-ones for evaluation of antimicrobial and anticancer activity . Part 2; Sanna P et al.; A new set of 35 3-alkyl and 3-ethoxycarbonylalkyl 6- and/or 7-substituted-2-quinoxalinones was prepared and submitted to a preliminary in vitro investigation of their antimicrobial, anticancer and anti-HIV activities . Results are referred. Phys Med Rehabil Clin N Am, 1999 May, 10(2), 403 - 36, ix Antimicrobial agents; Embil JM et al.; This article employs a comprehensive approach to review antimicrobial drugs, emphasizing the strengths and limitations of drugs including the traditional, those newly introduced and those currently under development . The significant issue of antimicrobial resistant organisms is addressed specifically. Trends Biotechnol, 1999 Jul, 17(7), 275 - 81 Integrated pathway-genome databases and their role in drug discovery; Karp PD et al.; Integrated pathway-genome databases describe the genes and genome of an organism, as well as its predicted pathways, reactions, enzymes and metabolites . In conjunction with visualization and analysis software, these databases provide a framework for improved understanding of microbial physiology and for antimicrobial drug discovery . We describe pathway-based analyses of the genomes of a number of medically relevant microorganisms and a novel software tool that visualizes gene-expression data on a diagram showing the whole metabolic network of the microorganism. EMBO J, 1999 Jun 15, 18(12), 3380 - 91 A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF; Manfruelli P et al.; Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway . The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene . We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes . Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter . This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila . Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes . Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--> Toll-->Cactus-->Dorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells. Ann Pharmacother, 1999 May, 33(5), 576 - 8 Pseudotumor cerebri secondary to intermediate-dose cytarabine HCl; Fort JA et al.; OBJECTIVE: To describe a case of pseudotumor cerebri associated with the administration of intermediate-dose cytarabine . CASE SUMMARY: An 11-year-old Hispanic boy with acute myeloblastic leukemia developed symptoms of pseudotumor cerebri (headache, diplopia, photophobia, nausea, vomiting) after receiving chemotherapy including cytarabine . The patient improved after a lumbar puncture and treatment with prednisone and acetazolamide, and is now asymptomatic . DISCUSSION: Pseudotumor cerebri is a condition usually associated with obese women of child-bearing age . Case reports in pediatric patients are unusual . Several medications have been implicated in causing pseudotumor cerebri, including antimicrobials (tetracycline, naladixic acid), amiodarone, lithium carbonate, vitamin A and its derivatives, growth hormone, and corticosteroids . Chemotherapy agents reported to cause pseudotumor cerebri include busulfan with cyclophosphamide, and the combination of vinblastine, cisplatin, and bleomycin . Most of the information on medication-induced pseudotumor cerebri is in the form of case reports . Different mechanisms for causing this condition have been offered for individual medications . Most of these explanations involve fluid imbalance or interference with the Na+/K+ adenosine triphosphatase pump . Controlled studies are difficult because this condition is an unpredictable and rare occurrence . Cytarabine has frequently been associated with neurologic toxicities, but few reports of pseudotumor cerebri can be found . CONCLUSIONS: The exact cause of pseudotumor cerebri in this patient is unknown, but cytarabine seems a likely cause . The mechanism by which cytarabine could cause this reaction is unclear. Res Exp Med (Berl), 1999 Apr, 198(6), 325 - 39 Protective capacity of a IgM/IgA-enriched polyclonal immunoglobulin-G preparation in endotoxemia; Oesser S et al.; Animal experiments were carried out to investigate whether a protective effect can be achieved in endotoxemia by intravenous (i.v.) application of a polyclonal immunoglobulin preparation (IVIG-IgG/A/M) enriched with 12% IgM and 12% IgA . Following administration of IVIG-IgG/A/M (500 mg/kg), endotoxemia was induced by intraperitoneal inoculation of a sublethal dose (5x10(8) CFU/kg) of Escherichia coli (E . coli) and subsequent i.v . administration of an antimicrobial agent (Imipenem) . Plasma endotoxin activity, IL-6 activity, mean arterial pressure, and skeletal muscle oxygen pressure (tpO2) were measured at regular intervals over a total observation period of 7 h . Prophylactic administration of IVIG-IgG/A/M was found to significantly attenuate (P<0.01) the antibiotic-induced increase in endotoxin activity as compared to the albumin control group . Limited endotoxemia in the IgG/A/M group was associated with reduced levels of circulating IL-6 (P<0.01) . Both lipopolysaccharide-induced hypotension and depression of tissue oxygenation were attenuated (P<0.01) by pre-treatment with IVIG-IgG/A/M . The experimental results suggest that in endotoxemia the polyclonal immunoglobulin preparation has a prophylactic protective effect on the acute phase responses and reduces the cardiodepressant effects of E . coli septicaemia. Pediatr Res, 1999 Jun, 45(6), 785 - 94 Antimicrobial peptides as mediators of epithelial host defense; Huttner KM et al.; Mammalian epithelial surfaces are remarkable for their ability to provide critical physiologic functions in the face of frequent microbial challenges . The fact that these mucosal surfaces remain infection-free in the normal host suggests that highly effective mechanisms of host defense have evolved to protect these environmentally exposed tissues . Throughout the animal and plant kingdoms, endogenous genetically encoded antimicrobial peptides have been shown to be key elements in the response to epithelial compromise and microbial invasion . In mammals, a variety of such peptides have been identified, including the well-characterized defensins and cathelicidins . A major source of these host defense molecules is circulating phagocytic leukocytes . However, more recently, it has been shown that resident epithelial cells of the skin and respiratory, alimentary, and genitourinary tracts also synthesize and release antimicrobial peptides . Both in vitro and in vivo data support the hypothesis that these molecules are important contributors to intrinsic mucosal immunity . Alterations in their level of expression or biologic activity can predispose the organism to microbial infection . The regulatory and developmental aspects of antimicrobial peptide synthesis are discussed from a perspective that emphasizes the possible relevance to pediatric medicine. Toxicol Pathol, 1999 Jan-Feb, 27(1), 58 - 63 The toxicology of interleukin-12: a review; Car BD et al.; Recombinant murine interleukin (IL)-12 (rmIL-12) exhibits antitumor, antiviral, and antimicrobial activities and can modify allergic inflammatory reactions in animal models . Recombinant human IL-12 (rhIL-12) is currently in clinical trials for treatment of cancer, asthma, and viral hepatitis . Principally a phagocyte-derived cytokine, IL-12 targets natural killer cells and T lymphocytes, stimulating their activity and the secretion of interferon (IFN)-gamma . An understanding of the toxicology of IL-12, due in part to effects mediated by IFN-gamma, has emerged from preclinical safety and mechanistic studies and initial clinical trials . Target organs common to several animal species and humans include the lymphohematopoietic system, intestines, liver, and lung. Virology, 1999 Jun 5, 258(2), 375 - 81 Nitric oxide down-regulates Epstein-Barr virus reactivation in epithelial cell lines; Gao X et al.; Nitric oxide (NO), a mediator of biological functions, has an antimicrobial activity against a variety of pathogens including viruses . In this study, we found that a constitutive, low level of inducible NO synthase (iNOS) mRNA was expressed in the EBV-infected gastric tissue-derived GT38 and GT39 cell lines, by analysis with the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blotting . Treatment of these cells with a specific NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA), induced the immediate-early, EBV transactivator gene BZLF1 protein ZEBRA, suggesting a significant increase in EBV reactivation by L-NMMA . Northern blotting demonstrated that BZLF1 and BRLF1 transcripts were also induced by 12-O-tetradecanoylphorbol-13 acetate (TPA) . Meanwhile, constitutive expression of iNOS mRNA was inhibited by TPA . L-NMMA also enhanced TPA-induced expression of the BZLF1 gene . On the other hand, a NO donor, S-nitroso-N-acetylpenicillamine (SNAP), which releases NO in an aqueous solution, inhibited the TPA-induced BZLF1 gene expression in a dose-dependent manner at both mRNA and protein levels . These results demonstrated that NO is a regulatory factor in maintaining virus latency via inhibiting EBV reactivation in the infected epithelial cells . Planta Med, 1999 May, 65(4), 383 - 5 Shamimin: a new flavonol C-glycoside from leaves of Bombax ceiba; Faizi S et al.; Shamimin a new flavonol C-glycoside has been isolated as a pale yellow powder from the ethanolic extract of fresh, undried leaves of Bombax ceiba . Its structure has been elucidated as 2-(2,4,5-trihydroxyphenyl)-3,5,7-trihydroxy-6-C- glucopyranosyloxy-4H-1-benzopyran-4-one through extensive spectroscopic methods (IR, mass, 1H- and 13C-NMR), and 2D-NMR experiments . Shamimin showed antimicrobial activity against a few bacteria and fungi. J Vasc Nurs, 1999 Mar, 17(1), 17 - 23 Effect of povidone-iodine on wound healing: a review; Kramer SA; For the purpose of providing a summary of current clinical trials to determine whether povidone-iodine is beneficial or detrimental to wound healing, an integrated review was completed . Clinical trials were defined as any study that uses some concentration and form of povidone-iodine in a comparison or evaluation with other products or treatments resulting in an impact of povidone-iodine on wounds . The use of povidone-iodine for cleansing, irrigating, and dressing wounds is controversial . Wound healing is complex and requires safe and effective treatment modalities . Numerous in vitro and in vivo studies have been done with conflicting results on bactericidal effects and cytotoxicity of this antimicrobial agent . Human and animal in vivo studies in the last 10 years were used for this review because often the relevance of in vitro data in clinical conditions are questioned . The varied studies provide evidence that in most instances, povidone-iodine did not effectively promote good wound healing; in fact, most studies showed either impaired wound healing, reduced wound strength, or infection. Ann Surg, 1999 Jun, 229(6), 801 - 4; discussion 804-6 The epidemic of cocaine-related juxtapyloric perforations: with a comment on the importance of testing for Helicobacter pylori; Feliciano DV et al.; OBJECTIVE: This is a report of 50 consecutive patients with juxtapyloric perforations after smoking "crack" cocaine (cocaine base) at one urban public hospital . SUMMARY BACKGROUND DATA: Although the exact causal relation between smoking crack cocaine and a subsequent juxtapyloric perforation has not been defined, surgical services in urban public hospitals now treat significant numbers of male addicts with such perforations . This report describes the patient set, presentation, and surgical management and suggests a possible role for Helicobacter pylori in contributing to these perforations . METHODS: A retrospective chart review was performed, supplemented by data from the patient log in the department of surgery . RESULTS: From 1994 to 1998, 50 consecutive patients (48 men, 2 women) with a mean age of 37 had epigastric pain and signs of peritonitis a median of 2 to 4 hours (but up to 48 hours) after smoking crack cocaine . A history of chronic smoking of crack as well as chronic alcohol abuse was noted in all patients; four had a prior history of presumed ulcer disease in the upper gastrointestinal tract . Free air was present on an upright abdominal x-ray in 84% of patients, and all underwent operative management . A 3- to 5-mm juxtapyloric perforation, usually in the prepyloric area, was found in all patients . Omental patch closure was used in 49 patients and falciform ligament closure in 1 . Two patients underwent parietal cell vagotomy as well . In the later period of the review, antral mucosal biopsies were performed through the juxtapyloric perforation in five patients . Urease testing was positive for infection with H . pyonri in four, and these patients were prescribed appropriate antimicrobial drugs . CONCLUSIONS: Juxtapyloric perforations after the smoking of crack cocaine occur in a largely male population of drug addicts who are 8 to 10 years younger than the patient group that historically has perforations in the pyloroduodenal area . These perforations are usually 3 to 5 mm in diameter, and an antral mucosal biopsy for subsequent urease testing should be performed if the location and size of the ulcer allow this to be done safely . Omental patch closure is appropriate therapy for patients without a history of prior ulcer disease; antimicrobial therapy and omeprazole are prescribed when H . pylori is present. J Obstet Gynecol Neonatal Nurs, 1999 May-Jun, 28(3), 241 - 54 Neonatal skin care: the scientific basis for practice; Lund C et al.; OBJECTIVE: To review the literature addressing the care of neonatal skin . DATA SOURCES: Computerized searches in MEDLINE and CINAHL, as well as references cited in articles reviewed . Key concepts in the searches included neonatal skin differences; neonatal skin and care practices for skin integrity; neonatal skin and toxicity; permeability; and contact irritant sensitization . STUDY SELECTION: Articles and comprehensive works relevant to key concepts and published after 1963, with an emphasis on new findings from 1993 to 1999 . One hundred two citations were identified as useful to this review . DATA EXTRACTION: Data were extracted and organized under the following headings: anatomy and physiology of the skin; physiologic and anatomic differences in neonatal skin; nutritional deficiencies; skin care practices; and care of skin breakdown . DATA SYNTHESIS: Newborns' skin is at risk for disruption of normal barrier function because of trauma . In light of available evidence about differences in neonatal skin development, clinical practice guidelines are suggested for baths, lubrication, antimicrobial skin disinfection, and adhesive removal . In addition, basic care practices are suggested for maintaining skin integrity, reducing exposure to potentially toxic substances, and promoting skin health beyond the neonatal period . Preventive care recommendations are made for reducing trauma, protecting the skin's immature barrier function, and promoting skin integrity . CONCLUSIONS: This review generated evidence with which to create a new and comprehensive practice guideline for clinicians . Evaluation of the guideline is under way at 58 U.S . sites. Del Med J, 1999 Apr, 71(4), 181 - 4 Adult onset Still's disease presenting as aseptic meningitis in a young healthy female; Sisselman SG; A 20-year-old white female presented with symptoms of upper respiratory tract infection, meningeal signs, rash, and fever . Initial laboratory data revealed a leukocytosis and abnormal CSF . An initial working diagnosis of the Aseptic Meningitis Syndrome was made . She did not respond to antimicrobial therapy . All culture results and viral titers were negative . One week into her hospital course, the diagnosis of Adult Onset Still's Disease (AOSD) was made . Antibiotics were discontinued and nonsteroidal anti-inflammatory drugs (NSAIDS) begun . The patient showed marked improvement within 24 hours . This case reveals that AOSD is an important consideration in the differential diagnosis of Aseptic Meningitis . Meningeal signs and abnormal cerebrospinal fluid (CSF), both detected in this patient, are very rare occurrences in Still's disease. Conn Med, 1999 May, 63(5), 265 - 70 Clinical and laboratory evolution of a culture-confirmed case of human granulocytic ehrlichiosis; Hossain D et al.; A 74-year-old man from suburban New York City, who was hospitalized because of chest pain and fever, was diagnosed as having human granulocytic ehrlichiosis on the eighth hospital day . Although leukocyte and platelet counts were normal on admission, they fell to abnormally low values then normalized prior to specific therapy against the human granulocytic ehrlichiosis agent . Intracytoplasmic inclusions suggestive of Ehrlichia were observed in up to six percent of granulocytes, and the human granulocytic ehrlichiosis bacterium was cultured in an HL 60 human promyelocytic cell line . The patient improved dramatically within 24 hours of doxycycline treatment, after failing to improve on various beta lactam antimicrobial agents . He was discharged from the hospital 14 days after admission . Because human granulocytic ehrlichiosis was not diagnosed until his eight hospital day, clinical and laboratory parameters prior to specific treatment were available . This case illustrates the clinical and laboratory evolution of the infection with human granulocytic ehrlichiosis agent in humans. Anticancer Drug Des, 1999 Feb, 14(1), 47 - 60 Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives; Bailly C et al.; Four diphenylfuran derivatives possessing different dicationic terminal side chains were used to investigate sequence-specific binding to DNA and poisoning of human topoisomerase II . Footprinting experiments with a range of DNA substrates attest that all four drugs bind selectively to AT-rich sequences in DNA . However, the quantitative analysis of the footprinting profiles reveals significant differences in terms of AT-selectivity according to the nature of the basic side chains . Furimidazoline (DB60) shows a reduced capacity to interact selectively with A.T tetrads compared with furamidine (DB75) and the 3-pentyl-substituted diamidine analogue DB226 . DB244, for which the two amidine ends are substituted with a cyclopentyl group, exhibits the most pronounced AT specificity . It binds tightly to sites composed of at least four adjacent AT base pairs, such as 5'-TAAT, AATT and TTTT . At low concentrations (< 2 microM) DB60 is also capable of forming stable complexes with AT sites but at higher concentrations the binding becomes totally non-specific due to additional intercalation of drug molecules into GC-rich sequences . Nevertheless, DB60 is the only drug is the series which stabilizes DNA-topoisomerase II covalent complexes . This compound effectively promotes DNA cleavage by topoisomerase II whereas DB75, DB226 and DB244 have practically no effect . The topoisomerase II poisoning activity of DB60 correlates with its ability to intercalate into GC sites in DNA whereas the three other diphenylfurans essentially behave as typical AT-selective minor groove binders . The study suggests that the antimicrobial activity of the diphenylfurans, which are active against the Pneumocystis carinii pathogen (PCP), depends essentially on their capacity to recognize AT-rich DNA sequences rather than their ability to interfere with topoisomerase II . In contrast, the cytotoxicity of drugs like DB60 would be connected with the formation of intercalation complexes and the stimulation of DNA cleavage by human topoisomerase II. Fungal Genet Biol, 1999 Apr, 26(3), 163 - 8 Antimicrobial phytoprotectants and fungal pathogens: a commentary; Osbourn AE; Many plants produce antifungal secondary metabolites . These may be preformed compounds which are found in healthy plants and which may represent in-built chemical barriers to infection by potential pathogens (preformed antimicrobial compounds or phytoanticipins) . Alternatively they may be synthesized in response to pathogen attack as part of the plant defence response (phytoalexins) . If these molecules do play a role in protecting plants against pathogen attack, then successful pathogens are presumably able to circumvent or tolerate these defences . Strategies may include avoidance, enzymatic degradation, and/or nondegradative mechanisms . This review outlines the different ways in which fungal pathogens may counter the antifungal compounds produced by their host plants and summarizes the evidence for and against these compounds as antimicrobial phytoprotectants . Nat Struct Biol, 1999 Jun, 6(6), 521 - 5 The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction; Gourley DG et al.; The structures of enzymes catalyzing the reactions in central metabolic pathways are generally well conserved as are their catalytic mechanisms . The two types of 3-dehydroquinate dehydratase (DHQase) are therefore most unusual since they are unrelated at the sequence level and they utilize completely different mechanisms to catalyze the same overall reaction . The type I enzymes catalyze a cis-dehydration of 3-dehydroquinate via a covalent imine intermediate, while the type II enzymes catalyze a trans-dehydration via an enolate intermediate . Here we report the three-dimensional structures of a representative member of each type of biosynthetic DHQase . Both enzymes function as part of the shikimate pathway, which is essential in microorganisms and plants for the biosynthesis of aromatic compounds including folate, ubiquinone and the aromatic amino acids . An explanation for the presence of two different enzymes catalyzing the same reaction is presented . The absence of the shikimate pathway in animals makes it an attractive target for antimicrobial agents . The availability of these two structures opens the way for the design of highly specific enzyme inhibitors with potential importance as selective therapeutic agents. Anesteziol Reanimatol, 1999 Mar-Apr, (2), 45 - 8 {Empirical antimicrobial chemoprophylaxis and chemotherapy of infections in surgical patients}; Kostiuchenko AL; Philosophy of antibacterial chemotherapy (ACT) in threatened and developing infection in surgical patients is formulated, based on clinical experience and analysis of published reports . Indications for ACT and choice of drugs during and after various surgical interventions are discussed . A variant of a protocol of antibiotic therapy is presented . Errors and inaccuracies in ACT are discussed. Curr Biol, 1999 Jun 3, 9(11), R403 - 7 Multidrug resistance: Versatile drug sensors of bacterial cells; Lewis K; One way that bacteria resist antimicrobial agents involves 'drug sensors', proteins that bind a range of structurally unrelated antimicrobial drugs and induce expression of multidrug resistance pumps . The basis for drug recognition is now becoming clear from the recently determined crystal structure of a drug sensor. Annu Rev Immunol, 1999, 17, 297 - 329 The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids; Porcelli SA et al.; Recent studies have identified the CD1 family of proteins as novel antigen-presenting molecules encoded by genes located outside of the major histocompatibility complex . CD1 proteins are conserved in all mammalian species so far examined and are prominently expressed on cells involved in antigen presentation, which suggests a role in activation of cell-mediated immunity . This has now been confirmed by functional studies demonstrating the ability of CD1 proteins to restrict the antigen-specific responses of T cells in humans and mice . Identification of naturally occurring antigens presented by CD1 has revealed the surprising finding that these are predominantly a variety of foreign lipids and glycolipids, including several found prominently in the cell walls and membranes of pathogenic mycobacteria . Structural, biochemical, and biophysical studies support the view that CD1 proteins bind the hydrophobic alkyl portions of these antigens directly and position the polar or hydrophilic head groups of bound lipids and glycolipids for highly specific interactions with T cell antigen receptors . Presentation of antigens by CD1 proteins requires uptake and intracellular processing by antigen presenting cells, and evidence exists for cellular pathways leading to the presentation of both exogenous and endogenous lipid antigens . T cells recognizing antigens presented by CD1 have a range of functional activities that suggest they are likely to mediate an important component of antimicrobial immunity and may also contribute to autoimmunity and host responses against neoplastic cells. Am J Infect Control, 1999 Jun, 27(3), 279 - 84 Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Surveillance Report, data summary from January 1996 through December 1997: A report from the National Nosocomial Infections Surveillance (NNIS) System; Use of tunneled femoral catheters to prevent catheter-related infection . A randomized et al.; Reanimation Polyvalente, Hopital Saint Joseph, Paris, FranceBACKGROUND: The risk for catheter-related infection seems higher with femoral catheters than with catheters inserted at other sites . OBJECTIVE: To evaluate the effect of catheter tunneling on femoral catheter-related infection in critically ill patients . DESIGN: Randomized, controlled trial . SETTING: Three intensive care units at academic hospitals in Paris, France . PATIENTS: 345 adult patients requiring a femoral venous catheter for more than 48 hours . INTERVENTION: Tunneled or nontunneled femoral catheters . MEASUREMENTS: Time to occurrence of systemic catheter-related sepsis, catheter-related bloodstream infection, and quantitative catheter tip culture with a cutoff of 10(3) colony-forming units/mL . RESULTS: Of 345 randomly assigned patients, 336 were evaluable . Probable systemic catheter-related sepsis occurred in 15 of 168 patients who received a nontunneled femoral catheter (controls) and in 5 of 168 patients who received a tunneled femoral catheter (estimated absolute risk reduction, 6% {95% CI, 0.9% to 11%}) . Time to occurrence of catheter-related bloodstream infection was not significantly modified (relative risk, 0.28 {CI, 0.03 to 1.92}; P = 0.18); 3 events occurred in the control group and 1 event occurred in the tunneled-catheter group . After stratification by treatment center and adjustment for variables that were prognostic (use of broad-spectrum antimicrobial agents at catheter insertion) or imbalanced between both groups (mechanical ventilation at insertion), tunnelized catheterization reduced the proportion of patients who developed systemic catheter-related sepsis (relative risk, 0.25 {CI, 0.09 to 0.72}; P = 0.005) and positive quantitative culture of the catheter tip (relative risk, 0.48 {CI, 0.23 to 0.99}; P = 0.045) . CONCLUSION: The incidence of femoral catheter-related infections in critically ill patients can be reduced by using subcutaneous tunneling. Microbiol Mol Biol Rev, 1999 Jun, 63(2), 266 - 92 Pseudomonas syringae phytotoxins: mode of action, regulation, and biosynthesis by peptide and polyketide synthetases; Bender CL et al.; Coronatine, syringomycin, syringopeptin, tabtoxin, and phaseolotoxin are the most intensively studied phytotoxins of Pseudomonas syringae, and each contributes significantly to bacterial virulence in plants . Coronatine functions partly as a mimic of methyl jasmonate, a hormone synthesized by plants undergoing biological stress . Syringomycin and syringopeptin form pores in plasma membranes, a process that leads to electrolyte leakage . Tabtoxin and phaseolotoxin are strongly antimicrobial and function by inhibiting glutamine synthetase and ornithine carbamoyltransferase, respectively . Genetic analysis has revealed the mechanisms responsible for toxin biosynthesis . Coronatine biosynthesis requires the cooperation of polyketide and peptide synthetases for the assembly of the coronafacic and coronamic acid moieties, respectively . Tabtoxin is derived from the lysine biosynthetic pathway, whereas syringomycin, syringopeptin, and phaseolotoxin biosynthesis requires peptide synthetases . Activation of phytotoxin synthesis is controlled by diverse environmental factors including plant signal molecules and temperature . Genes involved in the regulation of phytotoxin synthesis have been located within the coronatine and syringomycin gene clusters; however, additional regulatory genes are required for the synthesis of these and other phytotoxins . Global regulatory genes such as gacS modulate phytotoxin production in certain pathovars, indicating the complexity of the regulatory circuits controlling phytotoxin synthesis . The coronatine and syringomycin gene clusters have been intensively characterized and show potential for constructing modified polyketides and peptides . Genetic reprogramming of peptide and polyketide synthetases has been successful, and portions of the coronatine and syringomycin gene clusters could be valuable resources in developing new antimicrobial agents. Eur J Clin Microbiol Infect Dis, 1999 Mar, 18(3), 225 - 7 Susceptibility testing of linezolid by two standard methods; Hamilton-Miller JM et al.; To determine to what extent methodological differences affect susceptibility testing parameters for linezolid, MICs and disk inhibition zones were compared using the methods described by the National Committee for Clinical Laboratory Standards and the British Society for Antimicrobial Chemotherapy for 198 strains of gram-positive cocci . Zones were 4-5 mm larger by the British Society for Antimicrobial Chemotherapy method, but MICs did not differ, except for pneumococci, which were more sensitive when the British Society for Antimicrobial Chemotherapy method was used . This is because incubation in CO2 depresses the activity of linezolid against this species only . Breakpoints for linezolid may need adjusting when testing is by other than National Committee for Clinical Laboratory Standards methods. Rheum Dis Clin North Am, 1999 May, 25(2), 269 - 82 The role of nitric oxide in articular cartilage damage; Lotz M; The production of large amounts of NO in vitro by cytokine-activated chondrocytes has been established . In vitro studies suggest that NO compromises chondrocyte survival . The role of NO in regulating matrix biosynthesis and degradation has received much attention . Most studies indicate that NO is at least partly responsible for IL-1-induced suppression of glycosaminoglycan and collagen synthesis . NO also may be involved as a mediator of IL-1-induced expression of MMP, mRNA, and protein and may contribute as an activator of the latent forms of the enzymes . Although the interaction of NO and prostaglandins is of considerable interest, current data are inconclusive with respect to the role of NO in the regulation of prostaglandin synthesis, although it seems clear that prostaglandin is not involved in NO synthesis . It is important to note that NO does have protective effects in cartilage and other tissues . Under certain conditions, NO may have anabolic and anticatabolic effects in cartilage . In other tissues, notably in skin and muscle, NO has been found to have a stimulatory role in extracellular matrix repair . In antimicrobial defense, in general, and in bacterial arthritis specifically, NO is an important protective molecule . Production of NO in arthritis-affected cartilage and synovium is a consistent feature of human and experimentally induced arthritis . The production of NO is associated with matrix degradation and chondrocyte apoptosis . The administration of NO synthase inhibitors in experimentally induced arthritis has resulted in reduction of synovial inflammation and destruction of cartilage and bone. Ear Nose Throat J, 1999 May, 78(5), 358 - 9, 362-4 Initial report of primary sinusitis caused by an atypical pathogen (Mycobacterium chelonae) in an immunocompetent adult; Spring PM et al.; Primary sinonasal infections caused by atypical mycobacteria are rare . In fact, only four examples of a primary nontuberculous mycobacterial etiology of paranasal sinusitis have been cited in the literature . The patients in all these cases were infected with the human immunodeficiency virus and, by definition, they all had acquired immunodeficiency syndrome . We present a report of an immunocompetent adult with a history of chronic sinusitis who consistently and repeatedly manifested a fast-growing, nonpigmented, atypical mycobacterium of the Runyon group IV category: Mycobacterium chelonae . The patient was successfully treated over a 3-year period with a combination of antimicrobial agents, multiple limited endoscopic sinus surgeries, and eventually a total globe-sparing maxillectomy . At this time, the patient is disease-free and has received no further treatment . This case represents the first report of an immunocompetent adult host with a primary atypical mycobacterial infection of the paranasal sinuses . It also demonstrates the multimodal nature of the treatment of atypical mycobacterial infections . We also discuss the Byzantine classification scheme relative to atypical mycobacteria, the disease process in the immunocompromised host, and the various treatment options. Diagn Microbiol Infect Dis, 1999 Jun, 34(2), 115 - 7 Actinomyces viscosus postoperative endophthalmitis; Scarano FJ et al.; Endophthalmitis, attributable to Actinomyces viscosus, developed in a 78-year-old man after cataract surgery . Postoperative endophthalmitis with this organism is a rare occurrence . This report emphasizes the importance of the Actinomyces species as potential eye pathogens and presents antimicrobial susceptibility data for the isolate. Biochemistry, 1999 Jun 1, 38(22), 7235 - 42 Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli; Wu M et al.; Antimicrobial cationic peptides are prevalent throughout nature as part of the intrinsic defenses of most organisms, and have been proposed as a blueprint for the design of novel antimicrobial agents . They are known to interact with membranes, and it has been frequently proposed that this represents their antibacterial target . To see if this was a general mechanism of action, we studied the interaction, with model membranes and the cytoplasmic membrane of Escherichia coli, of 12 peptides representing all 4 structural classes of antimicrobial peptides . Planar lipid bilayer studies indicated that there was considerable variance in the interactions of the peptides with model phospholipid membranes, but generally both high concentrations of peptide and high transmembrane voltages (usually -180 mV) were required to observe conductance events (channels) . The channels observed for most peptides varied widely in magnitude and duration . An assay was developed to measure the interaction with the Escherichia coli cytoplasmic membrane employing the membrane potential sensitive dye 3,5-dipropylthiacarbocyanine in the outer membrane barrier-defective E . coli strain DC2 . It was demonstrated that individual peptides varied widely in their ability to depolarize the cytoplasmic membrane potential of E . coli, with certain peptides such as the loop peptide bactenecin and the alpha-helical peptide CP26 being unable to cause depolarization at the minimal inhibitory concentration (MIC), and others like gramicidin S causing maximal depolarization below the MIC . We discuss the mechanism of interaction with the cytoplasmic membrane in terms of the model of Matsuzaki et al . {(1998) Biochemistry 37, 15144-15153} and the possibility that the cytoplasmic membrane is not the target for some or even most cationic antimicrobial peptides. Clin Chem Lab Med, 1999 Mar, 37(3), 281 - 6 Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process; Baveye S et al.; Lactoferrin is an iron-binding glycoprotein found in exocrine secretions of mammals and released from neutrophilic granules during inflammation . This review describes the biological roles of lactoferrin in host defence . Secreted lactoferrin exerts antimicrobial action either by chelation of iron or by destabilization of bacterial membranes . Furthermore, lactoferrin modulates the inflammatory process, mainly by preventing the release of cytokines from monocytes and by regulating the proliferation and differentiation of immune cells . Some of these activities are related to the ability of lactoferrin to bind lipopolysaccharides (LPS) with high affinity . Indeed, recent in vitro studies indicate that lactoferrin is able to compete with the LPS-binding protein for LPS binding and therefore to prevent the transfer of LPS to CD14 present at the surface of monocytes . Moreover, the prophylactic properties of lactoferrin against septicemia in vivo have been demonstrated . Taken as a whole, these observations strongly suggest that lactoferrin is one of the key molecules which modulate the inflammatory response. Am J Respir Crit Care Med, 1999 Jun, 159(6), 1742 - 6 Risk factors for developing pneumonia within 48 hours of intubation; Rello J et al.; Two hundred fifty intubated patients were followed during the first 48 h after intubation in order to identify potential risk factors for developing pneumonia within this period . Thirty-two developed pneumonia during this time . Univariate analysis established that large volume aspiration, presence of sedation, intubation caused by respiratory/cardiac arrest or decrease in the level of consciousness, emergency procedure, cardiopulmonary resuscitation (CPR), and Glasgow coma score < 9 were significantly associated with pneumonia . In contrast, prior infection and prior antimicrobial use were associated with a protective effect . Presence of subglottic secretion drainage and 15 other variables had no significant effect . Multivariate analysis selected CPR (odds ratio {OR} = 5.13, 95% confidence intervals {CI} = 2.14, 12.26) and continuous sedation (OR = 4.40, 95% CI = 1.83, 10.59) as significant risk factors for pneumonia, while antibiotic use (OR = 0.29, 95% CI = 0.12, 0.69) showed a protective effect . Our findings emphasize that risk factors for pneumonia change during the intubation period, and preventing pneumonia requires a combined approach. Leuk Lymphoma, 1999 Jun, 34(1-2), 167 - 70 High dose methyl prednisolone in refractory chronic lymphocytic leukaemia; Thornton PD et al.; We treated 14 patients with advanced, resistant chronic lymphocytic leukaemia (CLL) including three with >10% prolymphocytes (CLL/PL) with high dose methyl prednisolone (HDMP) . All patients had stage C CLL or bulky stage B disease . There were 11 males and 3 females with a median age of 58.5 years (range: 49-69) . Six out of eleven CLL patients had a partial response as defined by the NCI guidelines, no patient had a complete remission . The mean duration of PR was 19.6 months with a median of 8 months (range 6-78) . Seven patients have died including the 5 non-responders . None of the 3 patients with CLL/PL had a measurable response . Previous treatments included chlorambucil, fludarabine, deoxycoformycin, anthracycline containing regimens such as CHOP and Campath-1H . HDMP was given at a dose of 1 g/m2 for five days, at monthly intervals for one to seven courses depending on the response . H2 antagonists and antimicrobial prophylaxis were given concurrently . Acyclovir prophylaxis was given if there was a recent history of herpes infection . HDMP was generally well tolerated . Side effects included fluid retention, hyperglycaemia, bradycardia (1 patient), herpes simplex (1), and pneumonia (1) in a patient with a previous history of recurrent chest infection and pneumonia . These results suggest that HDMP may be beneficial in the treatment of refractory CLL but is of no value in CLL/PL. Medicina (B Aires), 1999, 59(1), 59 - 62 {Diagnosis and treatment of spinal epidural abscess}; Roel JE et al.; Spinal epidural I abscess is an uncommon disease . The medical literature emphasizes the importance of its timely recognition and treatment . Three patients admitted in our hospital are presented . None of them was diagnosed on ambulatory bases . All of them were admitted because of spinal ache and two of them also had fever . Magnetic resonance imaging yielded the correct diagnosis in all cases and was very effective in delineating the extent of the lesion . We used antimicrobial therapy directed against the bacteria identified by cultures as well as surgical drainage in all cases . The three patients had a good outcome and no neurologic sequela . Early recognition, proper microbiologic diagnosis and surgical drainage are the main criteria for the current management of spinal epidural abscess. Antimicrob Agents Chemother, 1999 Jun, 43(6), 1387 - 92 Activities of beta-lactams and macrolides against Helicobacter pylori; Hassan IJ et al.; A continuous-culture system (chemostat) was used to study the activities of beta-lactam antimicrobial agents, clarithromycin, and 14-OH-clarithromycin against slowly growing Helicobacter pylori NCTC 11637 . H . pylori was grown to steady state before exposure to these antimicrobial agents at x8 the MIC . The bactericidal actions of combinations of amoxicillin and clarithromycin were also studied . Viable counts (numbers of CFU per milliliter) were determined at 2-h intervals for 12 h and at 20 h after the addition of antibiotics . The effects of pH changes (6.5 to 7.4) on the activities of amoxicillin, clarithromycin, and the combination of these against H . pylori NCTC 11637 were also studied . Viable counts following exposure to ampicillin, cefixime, ceftazidime, cefuroxime, cefotaxime, azlocillin, and piperacillin at 20 h showed bacteriostatic activity . Imipenem, meropenem, amoxicillin, clarithromycin, and 14-OH-clarithromycin reduced the viable counts by 3 log10 CFU/ml (>/=99.9% killing) . Imipenem was the most rapidly bactericidal against H . pylori NCTC 11637 . Results of the pH experiments showed that amoxicillin was bactericidal at pHs 6.5 to 7 . 4 . Clarithromycin was bactericidal at pH 7.0 to 7.4 but was bacteriostatic at pH 6.5 . The combination of amoxicillin and clarithromycin was bactericidal at pHs 6.5 and 7.0 . A batch culture (flask system) was also used to investigate 12 strains of H . pylori for their susceptibilities to beta-lactams, clarithromycin, and/or 14-OH-clarithromycin in order to determine whether results from the chemostat model can be reproduced with batch cultures . Results of the chemostat time-kill kinetic study were reproducible in our batch culture flask system . The role of carbapenems in the eradication of H . pylori should be investigated. Antimicrob Agents Chemother, 1999 Jun, 43(6), 1347 - 9 Antimicrobial activities of amine- and guanidine-functionalized cholic acid derivatives; Li C et al.; Compounds in a series of cholic acid derivatives, designed to mimic the activities of polymyxin B and its derivatives, act as both potent antibiotics and effective permeabilizers of the outer membranes of gram-negative bacteria . Some of these compounds rival polymyxin B in antibacterial activity against gram-negative bacteria and are also very active against gram-positive organisms . Other compounds interact synergistically with hydrophobic antibiotics to inhibit bacterial growth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1999 May, 87(5), 544 - 51 Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters; Loury D et al.; OBJECTIVE: The purpose of this animal study was to determine whether IB-367, an antimicrobial peptide, is able to ameliorate oral mucositis by reducing microflora densities on the mucosal surfaces of the mouth . STUDY DESIGN: Oral mucositis was induced in hamsters by intraperitoneal injection of 5-fluorouracil followed by superficial abrasion of the buccal mucosa . A test formulation was applied topically to the buccal mucosa 5 or 6 times per day starting 6 to 8 hours before abrasion . RESULTS: Mucositis scores were significantly lower (P < .05) in hamsters given formulations containing 0.5 or 2.0 mg/mL of IB-367 than in placebo-treated controls . Treatment with IB-367 produced a more than 100-fold reduction in oral microflora densities . In a second experiment, treatment of hamsters with a formulation containing IB-367 at 0.12, 0.5 or 2.0 mg/mL resulted in a dose-dependent reduction in mucositis severity . CONCLUSION: The results indicate that reduction of local microflora densities through use of IB-367 may improve clinical outcomes in patients at risk for the development of oral mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1999 May, 87(5), 539 - 43 Levels of human defensin-1, an antimicrobial peptide, in saliva of patients with oral inflammation; Mizukawa N et al.; OBJECTIVE: The purpose of this study was to investigate the presence of an antimicrobial peptide, human defensin-1, in the saliva of patients with oral inflammation . STUDY DESIGN: Whole saliva samples were collected from patients with oral inflammation and from healthy volunteers . Human defensin-1 in saliva was isolated and purified by reversed-phase high-performance liquid chromatography . The amino acid sequence and molecular weight of defensin-1 were determined . The concentration of defensin-1 in saliva was quantified by high-performance liquid chromatography . Serum C-reactive protein concentration was measured by particle-enhanced turbidimetric immunoassay . RESULTS: The salivary defensin-1 concentration was significantly higher in patients with oral inflammation than in healthy volunteers; furthermore, in patients with oral inflammation, the concentration was significantly higher before treatment than after treatment . In the patients with oral inflammation, there was a strong positive correlation between salivary defensin-1 concentration and serum C-reactive protein concentration . CONCLUSIONS: The findings suggest that defensin-1 in saliva may be a convenient marker of inflammation associated with oral disease. J Antibiot (Tokyo), 1999 Mar, 52(3), 276 - 80 Lactonamycin, a new antimicrobial antibiotic produced by Streptomyces rishiriensis MJ773-88K4 . II . Structure determination; Matsumoto N et al.; The absolute structure of a new antibiotic lactonamycin is described . The NMR studies deduced one of four possible structures for the aglycon attached by a rhodinose through glycosidic bond . The stereochemistry of the sugar obtained by an acid hydrolysis was determined to be L-form by measuring optical rotation . The stereochemistry of the aglycon was determined by X-ray crystallographic analysis. J Med Chem, 1999 May 20, 42(10), 1816 - 22 Synthesis, mode of action, and biological activities of rebeccamycin bromo derivatives; Moreau P et al.; Bromo analogues of the natural metabolite rebeccamycin with and without a methyl substituent on the imide nitrogen were synthesized . The effects of the drugs on protein kinase C, the binding to DNA, and the effect on topoisomerase I were determined . The drugs' uptake and their antiproliferative activities against P388 leukemia cells sensitive and resistant to camptothecin, their antimicrobial activity against a Gram-positive bacterium (B . cereus), and their anti-HIV-1 activity were measured and compared to those of the chlorinated and dechlorinated analogues . Dibrominated imide 5 shows a remarkable activity against topoisomerase I, affecting both the kinase and DNA cleavage activity of the enzyme . The marked cytotoxic potency of this compound depends essentially on its capacity to inhibit topoisomerase I. Electrophoresis, 1999 Apr-May, 20(4-5), 775 - 80 Effects of interferon gamma on Chlamydia trachomatis serovar A and L2 protein expression investigated by two-dimensional gel electrophoresis; Shaw AC et al.; Chlamydia trachomatis is an obligate intracellular bacterium causing human ocular and genital disease . The lymphokine interferon gamma (IFN-gamma) is an important immune effector exerting antimicrobial effects towards several intracellular parasites, the chlamydia included . IFN-gamma has been reported to inhibit the chlamydial replication in vitro in part by depleting intracellular levels of tryptophan in a dose-dependent manner . In addition, down-regulation of important immunogens has been described . These findings are extended in this paper, in which we are combining pulse labeling with {35S}methionine and two-dimensional gel electrophoresis with immobilized pH gradients in order to investigate changes in the protein expression of C . trachomatis serovar A and L2 caused by treatment with IFN-gamma . In contrast to what was observed in C . trachomatis L2, our results showed that, in C . trachomatis A, down-regulations of the chlamydia major outer membrane protein and of several other proteins were detectable upon IFN-gamma treatment . In addition, we report the up-regulations of C . trachomatis A and L2 proteins with molecular masses of approximately 30 kDa and 40 kDa which may be part of an, as yet, uncharacterized chlamydial response to IFN-gamma treatment. PDA J Pharm Sci Technol, 1999 Jan-Feb, 53(1), 40 - 3 Rat ultrasound model for measuring pain resulting from intramuscularly injected antimicrobials; Dinh HK et al.; Rats emit ultrasonic vocalizations in situations involving anxiety or stress, defense, and submission . This study demonstrates the use of ultrasonic vocalizations as a quantitative measure of pain associated with intramuscular (i.m.) injections . Intramuscularly administered cephalosporins used in a comparative evaluation of pain in humans were chosen to validate this rat model . Three groups of four rats each received an intramuscular injection of either drug first, and then placebo, or placebo and then drug . The three drugs used in this study were cefonicid, cefoxitin, and cefamandole; saline was used as the placebo . Ultrasonic vocalizations were measured from 20 kHz to 100 kHz . The number of vocalizations ranged from 50 milliseconds to 500 milliseconds and most of the vocalizations occurred between 60 kHz and 80 kHz . Rats injected with cefoxitin, cefamandole, cefonicid, and saline vocalized an average of 36 +/- 11, 33 +/- 9, 28 +/- 7, and 11 +/- 6 times respectively . The response to all three antimicrobials differed significantly when compared with placebo (p < 0.01), however, there was no significant difference between the number of vocalizations for each antimicrobial injection . Further research may allow the correlation of the total duration of each vocalization, with the individual frequencies such as the 22 kHz and the 55 kHz components and with the amount of pain associated with the injection . This correlation could then be used to further identify differences in the amount of pain associated with each antimicrobial injection without increasing the sample size. J Burn Care Rehabil, 1999 May-Jun, 20(3), 195 - 200 Comparative evaluation of the antimicrobial activity of ACTICOAT antimicrobial barrier dressing; Yin HQ et al.; This study evaluated the antimicrobial activity of ACTICOAT Antimicrobial Barrier Dressing (Westaim Biomedical Corp, Fort Saskatchewan, Alberta, Canada), a silver-coated wound dressing, and compared it with silver nitrate, silver sulfadiazine, and mafenide acetate . The minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), zone of inhibition, and killing curves were determined with 5 clinically relevant bacteria . The data indicate that ACTICOAT silver had the lowest MIC and MBC and generated similar zones of inhibition to silver nitrate and silver sulfadiazine . Viable bacteria were undetectable 30 minutes after inoculation with the dressing, whereas it took 2 to 4 hours for silver nitrate and silver sulfadazine to achieve the same result . Mafenide acetate generated the biggest zones of inhibition, but it had the highest MICs and MBCs, and a significant number of bacteria still survived after 6 hours of treatment . The results suggest that ACTICOAT Antimicrobial Barrier Dressing has better antimicrobial performance than either of the existing silver-based products . ACTICOAT dressing killed the bacteria that were tested much faster, which is a very important characteristic for a wound dressing acting as a barrier to invasive infection to have . The study also suggests that a single susceptibility test such as a MIC or zone of inhibition test does not provide a comprehensive profile of antimicrobial activity of a topical antimicrobial agent or dressing . A combination of tests is desirable. Contraception, 1999 Jan, 59(1), 67 - 70 Reactive oxygen intermediates and reactive nitrogen intermediates in copper intrauterine device users; Anjalika et al.; The mechanism of action of copper in copper intrauterine devices (Cu IUD) as an antimicrobial agent is not well understood . Copper and iron are supposed to be responsible for release of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), which are very active in the presence of infection . The copper in a copper IUD could be responsible for limiting pelvic inflammatory disease . The present study was composed of 20 IUD seekers in whom ROI and RNI were studied before insertion of Cu IUD and then at 1, 4, and 12 weeks afterward . ROI showed a rise after insertion, whereas RNI showed a steady decline . Hence, it is presumed that the rise in ROI could be responsible for both the bactericidal effect of Cu IUD and also for the fall in RNIPIP: There is evidence of an increase in the number of polymorphonuclear leukocytes in the endometrium after insertion of a copper IUD . When activated, these macrophages secrete two groups of toxic metabolites that interact with each other: reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) . The mechanism of action of the copper in copper IUDs as an antimicrobial agent is not well understood . The present study measured ROI and RNI levels in 20 copper IUD users from Chandigarh, India, before and 1, 4, and 12 weeks after insertion . A statistically significant decrease in RNI levels was observed at each postinsertion time . In contrast, ROI levels showed an initial fall at 1 week postinsertion followed by a rise at 4 and 12 weeks . Control of infection has been found to be associated with this pattern of a rise in ROI and fall in RNI . (The initial fall in ROI at 1 week observed in the present study is assumed to be an anomaly related to the introduction of microbials during IUD insertion.) The copper in a copper IUD could be responsible for limiting pelvic inflammatory infection . Emerg Infect Dis, 1999 May-Jun, 5(3), 471 - 6 Bacterial resistance to ciprofloxacin in Greece: results from the National Electronic Surveillance System . Greek Network for the Surveillance of Antimicrobial Resistance; Vatopoulos AC et al.; According to 1997 susceptibility data from the National Electronic System for the Surveillance of Antimicrobial Resistance, Greece has high rates of ciprofloxacin resistance . For most species, the frequency of ciprofloxacin-resistant isolates (from highest to lowest, by patient setting) was as follows: intensive care unit > surgical > medical > outpatient . Most ciprofloxacin-resistant strains were multidrug resistant. Emerg Infect Dis, 1999 May-Jun, 5(3), 454 - 7 Application of data mining to intensive care unit microbiologic data; Moser SA et al.; We describe refinements to and new experimental applications of the Data Mining Surveillance System (DMSS), which uses a large electronic health-care database for monitoring emerging infections and antimicrobial resistance . For example, information from DMSS can indicate potentially important shifts in infection and antimicrobial resistance patterns in the intensive care units of a single health-care facility. Br J Ophthalmol, 1999 Jun, 83(6), 737 - 41 Antimicrobial defensin peptides of the human ocular surface; Haynes RJ et al.; BACKGROUND/AIMS: The antimicrobial activity of the tear film exceeds the activity of its known constituents . The authors postulate that this excess activity is the result of antimicrobial peptides called defensins, and they aimed to look for defensins in the human eye . METHODS: Evidence of defensin production was sought by reverse transcriptase polymerase chain reaction (RT-PCR) . Intron spanning primers were designed for beta defensins 1 and 2, and alpha defensins 5 and 6 . RT-PCR was performed on cornea, conjunctiva, and lacrimal gland samples, and reaction products were size fractionated and sequenced to confirm their identity . A monoclonal antibody was utilised for the detection of alpha defensins 1, 2, and 3 in tissue sections and in immunoblots of tears . RESULTS: RT-PCR revealed beta defensin 1 message in samples of conjunctiva, cornea, and lacrimal gland . beta Defensin 2 message was detected in the conjunctiva and cornea but was absent from the lacrimal gland . alpha Defensin 5 and 6 message was absent in these tissues but alpha defensins 1, 2, and 3 were detected in normal tears, lacrimal gland, and inflamed conjunctiva by immunochemistry . CONCLUSION: The data suggest the human eye innately produces a spectrum of antimicrobial defensin peptides . Defensins hold therapeutic potential in ocular infections as they have a broad spectrum of antimicrobial activity (bacteria fungi and viruses ) and accelerate epithelial healing. Hosp Pract (Off Ed), 1999 May 15, 34(5), 95 - 101 Antibiotic troubleshooting in primary care; Czachor JS; Allergic reactions, adverse effects, and drug interactions are an inevitable part of antimicrobial prescribing . A working knowledge of these issues remains paramount, especially when administering such agents to patients who are pregnant, infected with HIV, or who have renal insufficiency . The discussion also includes antibiotic-OTC drug interactions and antibiotic hypersensitivity. Int J Health Care Qual Assur Inc Leadersh Health Serv, 1998, 11(6-7), viii - xi Antimicrobial resistance: the threat to health and health care; Granitto K; This article addresses antimicrobial resistance and the threat it poses to an individual's health and the health care system . Diseases, such as pneumococcus have gained an overabundance of antimicrobial resistance . In addition, previously unknown diseases are surging and sounding alarm bells worldwide . The history and causes of this surge are examined globally . One such cause is the overuse of antibiotics in long-term care facilities . International strategies that have been implemented by organizations, such as the World Health Organization, to control the spread of infectious diseases, are also reviewed . The prevalence, causes and consequences of antibiotic resistant organisms, are found in long-term care facilities and hospitals specifically in Canada, are reviewed . Recommendations are made. Manag Care Interface, 1998 Dec, 11(12), 65 - 7 Pediatric otitis media; Julien DK et al.; The pediatric patients with routine, easiest-to-treat otitis media utilize 2.1 office visits during the course of a PTE . This patient group also received 0.13 tests, 0.14 laboratory and pathology services, and 0.05 medical/surgical procedures during the course of a PTE . Though 29.2% of these patients did not produce a claim for prescription drug therapy, this patient group received at least 1.53 prescriptions per PTEs . One prescription drug group was used in 39.8% of all PTEs . Of the PTEs treated with a single drug group, at least 56.4% were treated with amoxicillin . Two prescription drug groups were used in 18.1% of the PTEs . The prescribing patterns of physicians using two drug groups demonstrate a wide variety of switching patterns, some of which may have cost-of-care implications . Though surgical procedures are seldom utilized in SOI-1, approximately one-half of SOI-2 PTEs undergo some type of surgical procedure . The most common surgical procedure was myringotomy with the PE-TM tubes, which represents 82% of procedures performed on SOI-2 patients . The major cost drivers in the treatment of otitis media are clinical visits and antimicrobial drugs. Infect Immun, 1999 Jun, 67(6), 2740 - 5 Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands; Mathews M et al.; beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at mucosal surfaces . Two human beta-defensins, HBD-1 and HBD-2, were discovered in 1995 and 1997, respectively . However, little is known about the expression of HBD-1 or HBD-2 in tissues of the oral cavity and whether these proteins are secreted . In this study, we characterized the expression of HBD-1 and HBD-2 mRNAs within the major salivary glands, tongue, gingiva, and buccal mucosa and detected beta-defensin peptides in salivary secretions . Defensin mRNA expression was quantitated by RNase protection assays . HBD-1 mRNA expression was detected in the gingiva, parotid gland, buccal mucosa, and tongue . Expression of HBD-2 mRNA was detected only in the gingival mucosa and was most abundant in tissues with associated inflammation . To test whether beta-defensin expression was inducible, gingival keratinocyte cell cultures were treated with interleukin-1beta (IL-1beta) or bacterial lipopolysaccharide (LPS) for 24 h . HBD-2 expression increased approximately 16-fold with IL-1beta treatment and approximately 5-fold in the presence of LPS . Western immunoblotting, liquid chromatography, and mass spectrometry were used to identify the HBD-1 and HBD-2 peptides in human saliva . Human beta-defensins are expressed in oral tissues, and the proteins are secreted in saliva; HBD-1 expression was constitutive, while HBD-2 expression was induced by IL-1beta and LPS . Human beta-defensins may play an important role in the innate defenses against oral microorganisms. FEBS Lett, 1999 Apr 23, 449(2-3), 221 - 4 Interactions of an antimicrobial peptide, magainin 2, with lipopolysaccharide-containing liposomes as a model for outer membranes of gram-negative bacteria; Matsuzaki K et al.; F12W-magainin 2 preferentially interacted with lipopolysaccharide-containing bilayers, permeabilizing the membranes, compared with lipopolysaccharide-free phosphatidylcholine vesicles . Using this system, we demonstrated for the first time that the magainin peptide forms a helix upon binding to lipopolysaccharide . Incorporation of lipid A into phosphatidylcholine liposomes also enhanced interactions with the peptide . The presence of Mg2+, which nullifies the peptide's antibacterial activity against gram-negative bacteria, again weakened the interactions between the peptide and lipopolysaccharide-doped bilayers . This system seems to be useful for investigating the molecular details of peptide-lipopolysaccharide interactions. FEBS Lett, 1999 Apr 23, 449(2-3), 93 - 100 The non-enzymatic microbicidal activity of lysozymes; During K et al.; T4 lysozyme was thought to destroy bacteria by its muramidase activity . However, we demonstrate here that amphipathic helix stretches in the C-terminus of T4 lysozyme mediate its bactericidal and fungistatic activities . In heat-denatured T4 lysozyme, the enzymatic activity is completely abolished but unexpectedly, the antimicrobial functions remain preserved . Small synthetic peptides corresponding to amphipathic C-terminal domains of T4 lysozyme show a microbicidal activity . Its membrane disturbing activity was directly demonstrated for bacterial, fungal and plant cells but not in a hemolysis assay . Comparable results were obtained with hen egg white lysozyme . This opens up many new opportunities for optimization of lysozymes as antimicrobial agents in various applications by protein engineering. Adv Exp Med Biol, 1999, 464, 91 - 105 Combinatorial chemistry and its applications in agriculture and food; Wong DW et al.; Combinatorial chemistry has become a major focus of research activity in the pharmaceutical industry for development new therapeutic compounds . The same techniques could be potentially applied to benefit agricultural and food research . This article reviews the various procedures used in combinatorial chemistry, outlines some of the strengths and limitations of the various methods, and proposes potential areas in agriculture and food that could be benefited by this technology . These areas include developing new antimicrobial agents, antioxidants, and other additives, creating antigen-binding molecules for the detection or removal of food pathogens or toxicants, engineering food proteins and enzymes for specific functions, and modifying biosynthetic pathways for the production of novel natural products. Adv Exp Med Biol, 1999, 459, 145 - 59 Lysinoalanine in food and in antimicrobial proteins; Friedman M; Heat and alkali treatment of food proteins widely used in food processing results in the formation of crosslinked amino acids such as lysinoalanine, ornithinoalanine, lanthionine, and methyl-lanthionine and concurrent racemization of L-amino acid isomers to D-analogues . The mechanism of lysinoalanine formation is a two-step process: first, hydroxide ion-catalyzed elimination of cysteine and serine residues to a dehydroalanine intermediate; second, reaction of the double bond of dehydroalanine with the epsilon-NH2 group of lysine to form a lysinoalanine crosslink . The corresponding elimination-addition reaction of threonine produces methyl-dehydroalanine, which then reacts with the NH2 and SH groups to form methyl-lysinoalanine and methyl-lanthionine, respectively . The crosslinked amino acids lanthionine and methyl-lanthionine are formed by analogous nucleophilic addition reactions of the SH group of cysteine to dehydroalanine and methyl-dehydroalanine, respectively . Processing conditions that favor these transformations include high pH, temperature and exposure time . Factors which minimize lysinoalanine formation include the presence of SH-containing amino acids such as cysteine, N-acetyl-cysteine, and glutathione, dephosphorylation of O-phosphoryl esters, and acylation of epsilon-NH2 groups of lysine side chains . The presence of lysinoalanine residues along a protein chain decreases digestibility and nutritional quality in rodents but enhances nutritional quality in ruminants . Protein-bound and free lysinoalanines are reported to induce enlargement of nuclei of rat kidney cells . All of the mentioned dehydro and crosslinked amino acids also occur naturally in certain peptide and protein antibiotics . These include duramycin, cinnamycin, epidermin, subtilin and the widely used food preservative nisin . Mechanistic rationalizations are offered for the observed antimicrobial activities of these compounds in relation to their structures . The cited findings and new research to better define the chemistry and dietary and antimicrobial roles of lysinoalanine and related compounds should lead to better and safer foods. Anticancer Drug Des, 1998 Dec, 13(8), 981 - 93 Antineoplastic agents 393 . Synthesis of the trans-isomer of combretastatin A-4 prodrug; Pettit GR et al.; The (E)-stilbene isomer (2a) of the (Z)-combretastatin A-4 prodrug (1b) was efficiently prepared from (E)-combretastatin A-4 by a reaction sequence employing phosphorylation (dibenzyl chlorophosphite), cleavage (trimethyliodosilane) of the benzyl ester and reaction of the resulting phosphoric acid with sodium methoxide . The sodium phosphate product (2c) was also found to be an important side-product, presumably from iodine-catalyzed isomerization, when the analogous synthetic route was used to obtain the combretastatin A-4 prodrug (1b) . The phosphoric acid precursor of prodrug 1b derived from (Z)-combretastatin A-4 (1a) was converted into a series of metal cation and ammonium cation salts to evaluate effects on human cancer cell growth, antimicrobial activities and solubility behavior. Biopolymers, 1998, 47(6), 479 - 91 Plant defense peptides; Garcia-Olmedo F et al.; Eight families of antimicrobial peptides, ranging in size from 2 to 9 kD, have been identified in plants . These are thionins, defensins, so-called lipid transfer proteins, hevein- and knottin-like peptides, MBP1, IbAMP, and the recently reported snakins . All of them have compact structures that are stabilized by 2-6 disulfide bridges . They are part of both permanent and inducible defense barriers . Transgenic overexpression of the corresponding genes leads to enhanced tolerance to pathogens, and peptide-sensitive pathogen mutants have reduced virulence. Biopolymers, 1998, 47(6), 465 - 77 Cysteine-rich antimicrobial peptides in invertebrates; Dimarcq JL et al.; Antimicrobial peptides are pivotal elements of the innate immune defense against bacterial and fungal infections . Within the impressive list of antimicrobial peptides available at present, more than half have been characterized in arthropods . Cysteine-rich antimicrobial peptides represent the most diverse and widely distributed family among arthropods and, to a larger extent, among invertebrates . Proeminent groups of cysteine-rich peptides are peptides with the CS alpha beta motif and peptides forming an hairpin-like beta-sheet structure . Although these substances exhibit a large structural diversity and a wide spectrum of activity, they have in common the ability to permeabilize microbial cytoplasmic membranes . Drosophila has proved a remarkable system for the analysis of the regulation of expression of gene encoding antimicrobial cysteine-rich peptides . These studies have unraveled the striking parallels that exist between insect immunity and innate immunity in mammals that point to a common ancestry of essential aspects of innate immunity. Biopolymers, 1998, 47(6), 451 - 63 Mode of action of linear amphipathic alpha-helical antimicrobial peptides; Oren Z et al.; The increasing resistance of bacteria to conventional antibiotics resulted in a strong effort to develop antimicrobial compounds with new mechanisms of action . Antimicrobial peptides seem to be a promising solution to this problem . Many studies aimed at understanding their mode of action were described in the past few years . The most studied group includes the linear, mostly alpha-helical peptides . Although the exact mechanism by which they kill bacteria is not clearly understood, it has been shown that peptide-lipid interactions leading to membrane permeation play a role in their activity . Membrane permeation by amphipathic alpha-helical peptides can proceed via either one of the two mechanisms: (a) transmembrane pore formation via a "barrel-stave" mechanism; and (b) membrane destruction/solubilization via a "carpet-like" mechanism . The purpose of this review is to summarize recent studies aimed at understanding the mode of action of linear alpha-helical antimicrobial peptides . This review, which is focused on magainins, cecropins, and dermaseptins as representatives of the amphipathic alpha-helical antimicrobial peptides, supports the carpet-like rather the barrel-stave mechanism . That these peptides vary with regard to their length, amino acid composition, and next positive charge, but act via a common mechanism, may imply that other linear antimicrobial peptides that share the same properties also share the same mechanism. Biopolymers, 1998, 47(6), 435 - 50 Antimicrobial peptides from amphibian skin: what do they tell us? Simmaco M, Mignogna G, Barra D. Amphibian skin secretions contain many biologically active compounds, such as biogenic amines, complex alkaloids, or peptides . Within the latter class of molecules, a large number of peptide antibiotics has been isolated and characterized from different amphibian species . Antimicrobial peptides are considered the effector molecules of innate immunity, acting as a first line of defense against bacterial infections, by perturbing the phospholipid bilayer of the target cell membrane . These gene-encoded molecules are synthesized as inactive precursors and in several cases their proparts were shown to have highly conserved structures . It has also been demonstrated that the promoter regions of inducible peptide antibiotics are often regulated by the transcriptional control machinery NF-kappa B/I kappa B alpha . In amphibia of Rana and Bombina genera, inhibition of transcription of the genes encoding antimicrobial peptides has been obtained by glucocorticoid treatment, which causes an increase of I kappa B alpha synthesis . Moreover, determination of the structure of a number of genes coding for antimicrobial peptides in amphibia has actually shown that their promoter regions contain recognition sites for nuclear factors. Biopolymers, 1998, 47(6), 415 - 33 Animal antimicrobial peptides: an overview; Andreu D et al.; Antibiotic peptides are a key component of the innate immune systems of most multicellular organisms . Despite broad divergences in sequence and taxonomy, most antibiotic peptides share a common mechanism of action, i.e., membrane permeabilization of the pathogen . This review provides a general introduction to the subject, with emphasis on aspects such as structural types, post-translational modifications, mode of action or mechanisms of resistance . Some of these questions are treated in depth in other reviews in this issue . The review also discusses the role of antimicrobial peptides in nature, including several pathological conditions, as well as recent accounts of their application at the preclinical level. Australas J Dermatol, 1999 May, 40(2), 103 - 5 Primary cutaneous nocardiosis; Lee MS et al.; A case of primary cutaneous nocardiosis due to Nocardia asteroides occurring in a steroid-dependent asthmatic with no history of trauma is presented . He had a 5 month history of painful nodules on his right shin and calf . He was initially treated with a 6 week course of oral cephalexin 500 mg four times daily, followed by a 2 week course of minocycline 100 mg twice daily with worsening of the infection . A 12 week course of oral clarithromycin 500 mg twice daily led to complete resolution . A discussion of the problems associated with antimicrobial susceptibility testing and nocardia resistance is presented. J Microbiol Methods, 1999 Apr, 35(3), 201 - 6 Antimicrobial activity of diterpene resin acid derivatives; Savluchinske Feio S et al.; C-13 deisopropylated and/or C-7 oxidized resin acid derivatives were tested against various microorganisms to determine structural features responsible for biological activity and to determine the influence of the C-13 isopropyl group on antimicrobial activity . Test results show that methyl cis and trans 7-oxo-13-deisopropyldehydroabietate and a mixture of both isomers exhibited activity against fungi and bacteria. Int J Periodontics Restorative Dent, 1997 Feb, 17(1), 41 - 51 Clinical results with exposed polyglactin 910 resorbable membranes for guided tissue regeneration; Urbani G et al.; Three cases are presented where early exposure of a resorbable membrane occurred during guided tissue regeneration therapy . An antimicrobial regimen was selected to determine whether infection of exposed membranes could be controlled to the point of achieving acceptable clinical results without membrane removal . The results suggest that with the use of the antimicrobial regimen: (1) exposure is compatible with successful clinical results, and (2) removal is not necessary. Can J Gastroenterol, 1999 Apr, 13(3), 243 - 9 Antibiotic resistance mechanisms of Helicobacter pylori; Hoffman PS; Infection with Helicobacter pylori is most frequently associated with gastritis and peptic ulcer disease . Antimicrobial intervention, together with proton pump inhibitors, has become the standard therapy for treating this disease . Resistance to clarithromycin and metronidazole, two of the most commonly used antimicrobials for treatment of H pylori infections, is often associated with treatment failures and relapse of infection . Clarithromycin resistance arises through mutations leading to base changes in 23S ribosomal RNA subunits, while resistance to metronidazole is due to mutations in the rdxA gene, which encodes a novel nitroreductase that is responsible for reductive activation of the drug . Products of metronidazole activation are mutagenic and can be demonstrated to increase both the mutation frequency and the frequency at which antibiotic resistance arises in H pylori. Pharmacotherapy, 1999 May, 19(5), 661 - 6 Mycobacterium fortuitum meningitis associated with an epidural catheter: case report and a review of the literature; Madaras-Kelly KJ et al.; Mycobacterium fortuitum is a rapidly growing organism that has rarely been associated with meningitis . A patient developed M . fortuitum meningitis as the result of a permanent indwelling, contaminated, epidural catheter . Diagnosis and treatment of the disease are difficult in that clinical features may be indolent, and many antimicrobials with activity against M . fortuitum have minimal cerebrospinal fluid penetration . This patient was cured with an antibiotic regimen that consisted of doxycycline, ciprofloxacin, imipenem, and clarithromycin, and removal of the epidural catheter. J Anim Sci, 1999 Apr, 77(4), 973 - 8 Bacterial flora of liver abscesses in feedlot cattle fed tylosin or no tylosin; Nagaraja TG et al.; Bacterial flora of liver abscesses from cattle fed tylosin or no tylosin and susceptibilities of the predominant bacterial isolates to tylosin and other antimicrobial compounds were determined . Abscessed livers were collected at slaughter from cattle originating from feedlots that had fed tylosin (n = 36) or no tylosin (n = 41) for at least 2 yr, and segments of livers with one or two intact abscesses were transported to the laboratory . Abscesses were cultured for anaerobic and facultative bacteria . Fusobacterium necrophorum, either as single culture or mixed with other bacteria, was isolated from all abscesses . The incidence of subsp . necrophorum, as part of the mixed infection, was lower (P < .05) in the tylosin group than in the no-tylosin group (33 vs 61%) . However, the incidence of Actinomyces pyogenes was higher (P < .01) in the tylosin group than in the no-tylosin group (53 vs 10%) . Totals of 119 F . necrophorum and 21 A . pyogenes isolates were used for determinations of susceptibilities to bacitracin, oxytetracycline, chlortetracycline, lasalocid, monensin, tylosin, tilmicosin, and virginiamycin . The minimum inhibitory concentrations (MIC) of antibiotics were determined with a broth microdilution method . The mean MIC of tylosin for F . necrophorum and A . pyogenes were not different between isolates from tylosin and no-tylosin groups . We concluded that continuous feeding of tylosin did not induce resistance in F . necrophorum or A . pyogenes . Also, the higher incidence of mixed infection of F . necrophorum and A . pyogenes in liver abscesses of tylosin-fed cattle suggests a potential synergistic interaction between the two organisms in causing liver abscesses. N Z Med J, 1999 Apr 9, 112(1085), 113 - 5 A significant increase in antimicrobial resistance among pneumococci causing invasive disease in New Zealand; Brett MS et al.; AIMS: To review the prevalence of antibiotic resistance and the distribution of capsular types among pneumococci from invasive disease in New Zealand from 1995 through 1997 . METHOD: Pneumococci isolated from sterile sites that were referred to the Institute of Environmental Science and Research (ESR) were tested for antimicrobial susceptibility and capsular type . RESULTS: A total of 994 pneumococci were referred by 27 hospital and community laboratories . Almost 74% of the isolates were from patients aged < 15 years or > or = 60 years . The majority (88.2%) of the isolates were from blood cultures . In 1997, cefotaxime-resistant pneumococci were confirmed for the first time from invasive disease in New Zealand . Over the three years, 6.0% of the pneumococci were penicillin-nonsusceptible (MIC > or = 0.12 mg/L) and 3.7% were cefotaxime-nonsusceptible (MIC > or = 1 mg/L) . Penicillin nonsusceptibility increased significantly from 1.9% in 1995 to 6.2% in 1996 and 9.9% in 1997 . Similarly, cefotaxime nonsusceptibility increased from 0.6% in 1995 to 3.5% in 1996 and 6.9% in 1997 . In descending order of frequency, the ten most common capsular types were 14, 19, 6, 9, 1, 4, 18, 7, 23, and 3 . Eighty-three percent of the penicillin-nonsusceptible pneumococci belonged to serotypes 9V, 19A, 19F, 23F, 14 and 6B and 90% belonged to serotypes included in the 23-valent vaccine . CONCLUSIONS: The increasing prevalence of antimicrobial resistance among pneumococci highlights the need for continued surveillance and for effective measures to prevent pneumococcal infections. Adv Wound Care, 1998 Nov-Dec, 11(7), 329 - 31 Diabetic foot infections: evaluation and management; Frykberg RG; Management of diabetic foot infections requires a thorough knowledge of the pathophysiology involved, the associated microbiological characteristics, and current diagnostic and treatment regiments . Management of the infected diabetic foot requires a combination of therapies including antimicrobial agents, surgical drainage, local wound care, and avoidance of weight-bearing . The complexities of this problem often require the input of multiple specialists working cohesively to manage the concurrent complications of the disease in general, as well as the foot lesion in particular. Br Med Bull, 1998, 54(3), 569 - 78 Multiple drug resistant tuberculosis: aetiology, diagnosis and outcome; Eltringham IJ et al.; Tuberculosis is an increasing problem worldwide both in terms of disease burden and resistance to conventional antibiotic therapy . Studies of outbreaks involving resistant strains have highlighted the need for both improved infection control and the rapid provision of accurate susceptibility data . Each patient should undergo a risk assessment for possible resistance and those in whom risk factors exist should be investigated by means of rapid molecular techniques or other phenotypic methods, so that appropriate management can be instituted with minimal delay . The ultimate outcome will vary according to whether the patient is immunosuppressed, the time taken to make a diagnosis, the severity of disease as well as the degree of resistance . The prognosis can be improved when adequate antibiotic therapy is started as soon as resistance is suspected . Adjuncts to conventional treatment, such as surgery and perhaps immunotherapy may be considered when response to antimicrobial chemotherapy has been suboptimal. Br Med Bull, 1998, 54(3), 523 - 32 Resurgent and emergent disease in a changing world; Cohen ML; Emerging infectious diseases pose important public health problems for both the developed and developing world . Many ne